Disclosed are methods, compounds and compositions useful for the prevention or reduction of human malodour, in particular human axillary malodour.
It is known that fresh sweat is odourless and that odour is only formed upon contact of sweat with skin bacteria (for example bacteria of the genera of Staphylococcus and Corynebacteria), and it is believed that odourless molecules present in sweat are degraded by bacteria colonizing the axilla. It is generally accepted that highly unpleasant malodour is released from fresh sweat mainly by the Corynebacteria genus of bacteria.
It has been suggested to treat malodour by eliminating the bacteria that are causing it. Indeed, commercially-available deodorants often contain antibacterial compounds that inhibit the growth of skin microflora over a broad range of species. Antibacterial compounds currently used in deodorant products include, for example, the broad band antibacterial and antimicrobial Triclosan (2,4,4′-trichloro-2′hydroxy-diphenyl-ether). However, a draw-back to the use of antibacterials is the potential for disturbing the equilibrium of the skin's natural microflora.
Fatty acids are known to play a role in axillary malodour, and are characterised by a particularly unpleasant smell. Alpha-N-acyl-glutamine substrates have been shown to be the main precursors of axilla malodour and they are cleaved by the enzyme N-α-acyl-glutamine-aminoacylase to form unpleasantly smelling fatty acids (A. Natsch et al., Journal of Biological Chemistry 2003, 278(8), 5718-5727).
The applicants have identified specific inhibitors of the enzyme (WO 02/092024). Among many other compound groups, these include alpha-N-acyl-L-glutamines or carbamates of L-glutamine.
The malodour precursor compounds are substrates that may generally be described as derivatives of L-glutamine, in particular L-glutamine derivatives wherein the alpha-N atom of the L-glutamine residue is acylated with a residue of a malodorous compound, in particular a fatty acid residue, more particularly a short chain, branched fatty acid residue. One example of such a precursor compound that was isolated from human sweat has the structure:

Cleavage of this substrate at the alpha-N position releases the 3-hydroxy-3-methyl-hexanoic acid, itself having a pungent odour, which dehydrates to give 3-methyl-3-hexenoic acid which is another key malodour volatile in human sweat.
The AMRE enzyme may cleave substrates for a wide variety of different smelling and non-smelling acids and other compounds. In addition to amide bonds, it may cleave carbamate bonds at the alpha-N position thereby mediating the release of an alcohol, CO2 and L-glutamine.
The applicants now have found that malodour can be significantly reduced by certain alternative substrates that reduce the formation of unpleasantly-smelling cleavage products and instead produce cleavage products that are neutral or olfactorily pleasant.